Linked Life Data

15173166

Source:http://linkedlifedata.com/resource/pubmed/id/15173166

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2004-8-9
pubmed:databankReference
pubmed:abstractText
WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34991-5000
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15173166-Amino Acid Sequence, pubmed-meshheading:15173166-Animals, pubmed-meshheading:15173166-DNA, Complementary, pubmed-meshheading:15173166-Drosophila, pubmed-meshheading:15173166-Drosophila Proteins, pubmed-meshheading:15173166-Drosophila melanogaster, pubmed-meshheading:15173166-Ligands, pubmed-meshheading:15173166-Magnetic Resonance Spectroscopy, pubmed-meshheading:15173166-Membrane Proteins, pubmed-meshheading:15173166-Models, Molecular, pubmed-meshheading:15173166-Molecular Sequence Data, pubmed-meshheading:15173166-Peptides, pubmed-meshheading:15173166-Phenylalanine, pubmed-meshheading:15173166-Protein Binding, pubmed-meshheading:15173166-Protein Structure, Tertiary, pubmed-meshheading:15173166-Receptors, Notch, pubmed-meshheading:15173166-Sequence Homology, Amino Acid, pubmed-meshheading:15173166-Spectrometry, Fluorescence, pubmed-meshheading:15173166-Tryptophan, pubmed-meshheading:15173166-Ubiquitin-Protein Ligases
pubmed:year
2004
pubmed:articleTitle
The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.
pubmed:affiliation
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P. O. Box 88, Manchester M60 1QD, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't